Genital tract infections caused by Chlamydia trachomatis are a leading cause of sexually transmitted diseases (STDs) Immunoprophylaxis is one way to control chlamydial caused STDs. Host immunity to chlamydial infections of the genital tract mucosae are poorly understood. This lack of understanding has hampered progress towards the development of an efficacious chlamydial vaccine. The goal of this project is to use a murine model of chlamydial genital tract infection to define those immune mechanisms that are important in acquired immunity to infection and to identify those chlamydial antigens which elicit protective immune responses. By using genetically defined knock out mice deficient in specific immune functions and adoptive immunization experiments we have shown that CD4+ T cells play a significant role in the acquired immune response to chlamydial infection. CD4+ T cells function in providing cognate help for antibody production (Th2) and in cell mediated immunity (Th1). Our data show that chlamydial specific serum or secretory antibody plays only a minor role in acquired immunity to chlamydial infection negating a critical role for chlamydial specific CD4+ Th2 cells in protective immunity. Conversely, Th1 cells are critical for the resolution of chlamydial infection and resistance to re-infection. The mechanism by which CD4+ Th1 cells function and those chlamydial antigens recognized by protective CD4+ Th1 cells are under investigation. Definition of the mechanism(s) by which CD4+ T cell subsets function in protective immunity and characterization of those chlamydial antigens recognized by such subsets will provide useful information for the design of subunit or recombinant vaccines for the prevention chlamydial infection of the genital tract mucosa.